RAB11FIP5 explained

Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.^{[1] [2] [3]}

Interactions

RAB11FIP5 has been shown to interact with RAB11A^{[4] [5]} and RAB25.^{[4] [5]}

Vesicle trafficking

Rab11FIP5 is one of the many proteins that have been shown to interact with the Rab11 protein.^[4] Rab GTPases, such as Rab11, are enzymes that are involved in vesicular trafficking. Rab11 specifically plays a key role in endocytic trafficking and recycling through guiding early endosomes to endosome recycling complexes.^[6] Rab11FIP5, like most other Rab11FIP proteins, interacts with Rab11 by serving as an adaptor protein. This leads to downstream changes with regards to which proteins can interact. This is a result of the various Rab11FIP proteins that each have different binding partners. This process allows for the coordination and organization of endosomal transport and ultimately gives Rab11 its versatile function in the cell. It is believed that Rab11 recruits specific Rab11FIP proteins to the surface of vesicles in order to determine how the vesicle will behave.^[7] Studies have shown that Rab11FIP5 localizes to the perinuclear endosomes where it aids in sorting vesicles into the slow recycling route.^[7] This process involves the transport of cargo proteins, like endocytosed receptors, to endosome recycling complexes and subsequently to the plasma membrane. This is in contrast to the fast constitutive recycling route which allows for the direct transport of cargo from the endosome to the plasma membrane.^[7] Rab11FIP5 aids in this sorting process by binding to kinesin II and forming a protein complex to regulate vesicular trafficking. Some of the proteins that are regulated through Rab11FIP5 mediated vesicle trafficking are microtubule proteins and the TfR receptor. This links Rab11FIP5 functionality to the cell cytoskeleton and the iron uptake of a cell, respectively.^[7]

Other functions

Rab11FIP5 has been shown to play a role in the nervous system because it functions in neurons. Studies have suggested that Rab11FIP5 is involved in regulating the localization of the postsynaptic AMPA-type glutamate receptor. The AMPA receptor is an excitatory receptor that can be found on the plasma membranes of neurons. Studies have shown that mice with the Rab11FIP5 gene knocked out have severe long term neuronal depression. Without the presence of Rab11FIP5, it is hypothesized that the internalized AMPA receptors cannot be recycled back onto the plasma membrane because the receptors cannot be correctly trafficked to intracellular organelles responsible for recycling.^[8] Rab11FIP5 has also been implicated as a protein involved in the creation of tissue polarity during development. Rab11FIP5 has been shown to be involved in the vesicle trafficking and degradation of proteins used to coordinate embryonic development. This is conducted in a manner that helps maintain the ectoderm polarity in embryonic Drosophila.^[9] Rab11FIP5 is also suggested to be involved in aiding salivary epithelial cells to adjust to extracellular pH. V-ATPase, a proton pump protein, has been shown to be reliant on Rab11FIP5 mediated vesicle trafficking. When Rab11FIP5 is knocked down, salivary cells cannot correctly translocate V-ATPase to the plasma membrane in response to extracellular acidosis. While this pathway remains largely unknown, these results suggest a link between Rab11FIP5 function and the maintenance of the buffering capacity of saliva.^[10]

Rab11FIP5 is also required for regulated exocytosis in neuroendocrine cells. Knockdown of Rab11FIP5 inhibited calcium-stimulated dense core vesicle (DCV) exocytosis in a neuroendocrine cell line BON cells. DCV membrane proteins are lost to the plasma membrane during exocytosis and recycle to the Golgi through the retrograde trafficking pathway. The requirement of Rab11FIP5 for regulated DCV exocytosis may be attributed to its role in endosome-mediated retrograde trafficking.^[11]

Further reading

• Wang D, Buyon JP, Zhu W, Chan EK . Defining a novel 75-kDa phosphoprotein associated with SS-A/Ro and identification of distinct human autoantibodies . The Journal of Clinical Investigation . 104 . 9 . 1265–75 . November 1999 . 10545525 . 409828 . 10.1172/JCI8003 .
• Chen D, Xu W, He P, Medrano EE, Whiteheart SW . Gaf-1, a gamma -SNAP-binding protein associated with the mitochondria . The Journal of Biological Chemistry . 276 . 16 . 13127–35 . April 2001 . 11278501 . 10.1074/jbc.M009424200 . free .
• Prekeris R, Davies JM, Scheller RH . Identification of a novel Rab11/25 binding domain present in Eferin and Rip proteins . The Journal of Biological Chemistry . 276 . 42 . 38966–70 . October 2001 . 11481332 . 10.1074/jbc.M106133200 . free .
• Hales CM, Griner R, Hobdy-Henderson KC, Dorn MC, Hardy D, Kumar R, Navarre J, Chan EK, Lapierre LA, Goldenring JR . Identification and characterization of a family of Rab11-interacting proteins . The Journal of Biological Chemistry . 276 . 42 . 39067–75 . October 2001 . 11495908 . 10.1074/jbc.M104831200 . free .
• Wallace DM, Lindsay AJ, Hendrick AG, McCaffrey MW . Rab11-FIP4 interacts with Rab11 in a GTP-dependent manner and its overexpression condenses the Rab11 positive compartment in HeLa cells . Biochemical and Biophysical Research Communications . 299 . 5 . 770–9 . December 2002 . 12470645 . 10.1016/S0006-291X(02)02720-1 .
• Tani K, Shibata M, Kawase K, Kawashima H, Hatsuzawa K, Nagahama M, Tagaya M . Mapping of functional domains of gamma-SNAP . The Journal of Biological Chemistry . 278 . 15 . 13531–8 . April 2003 . 12554740 . 10.1074/jbc.M213205200 . free .
• Kawase K, Shibata M, Kawashima H, Hatsuzawa K, Nagahama M, Tagaya M, Tani K . Gaf-1b is an alternative splice variant of Gaf-1/Rip11 . Biochemical and Biophysical Research Communications . 303 . 4 . 1042–6 . April 2003 . 12684040 . 10.1016/S0006-291X(03)00486-8 .
• Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC . Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry . Analytical Chemistry . 76 . 10 . 2763–72 . May 2004 . 15144186 . 10.1021/ac035352d .
• Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O'Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T . Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization . Current Biology . 14 . 16 . 1436–50 . August 2004 . 15324660 . 10.1016/j.cub.2004.07.051 . 2371325 . free . 2004CBio...14.1436J .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . November 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Schwenk RW, Luiken JJ, Eckel J . FIP2 and Rip11 specify Rab11a-mediated cellular distribution of GLUT4 and FAT/CD36 in H9c2-hIR cells . Biochemical and Biophysical Research Communications . 363 . 1 . 119–25 . November 2007 . 17854769 . 10.1016/j.bbrc.2007.08.111 .

Notes and References

1. Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 5 . 6 . 355–64 . December 1998 . 10048485 . 10.1093/dnares/5.6.355 . free .
2. Prekeris R, Klumperman J, Scheller RH . A Rab11/Rip11 protein complex regulates apical membrane trafficking via recycling endosomes . Molecular Cell . 6 . 6 . 1437–48 . December 2000 . 11163216 . 10.1016/S1097-2765(00)00140-4 . free .
3. Web site: Entrez Gene: RAB11FIP5 RAB11 family interacting protein 5 (class I).
4. Hales CM, Griner R, Hobdy-Henderson KC, Dorn MC, Hardy D, Kumar R, Navarre J, Chan EK, Lapierre LA, Goldenring JR . Identification and characterization of a family of Rab11-interacting proteins . The Journal of Biological Chemistry . 276 . 42 . 39067–75 . October 2001 . 11495908 . 10.1074/jbc.M104831200 . free .
5. Prekeris R, Davies JM, Scheller RH . Identification of a novel Rab11/25 binding domain present in Eferin and Rip proteins . The Journal of Biological Chemistry . 276 . 42 . 38966–70 . October 2001 . 11481332 . 10.1074/jbc.M106133200 . free .
6. Grant BD, Donaldson JG . Pathways and mechanisms of endocytic recycling . Nature Reviews Molecular Cell Biology . 10 . 9 . 597–608 . 2009 . 19696797 . 3038567 . 10.1038/nrm2755 .
7. Schonteich E, Wilson GM, Burden J, Hopkins CR, Anderson K, Goldenring JR, Prekeris R . The Rip11/Rab11-FIP5 and kinesin II complex regulates endocytic protein recycling . Journal of Cell Science . 121 . Pt 22 . 3824–33 . November 2008 . 18957512 . 10.1242/jcs.032441 . 4365997.
8. Bacaj T, Ahmad M, Jurado S, Malenka RC, Südhof TC . Synaptic Function of Rab11Fip5: Selective Requirement for Hippocampal Long-Term Depression . The Journal of Neuroscience . 35 . 19 . 7460–74 . May 2015 . 25972173 . 10.1523/JNEUROSCI.1581-14.2015 . 4429152.
9. Calero-Cuenca FJ, Sotillos S . Nuf and Rip11 requirement for polarity determinant recycling during Drosophila development . Small GTPases . 9 . 4 . 352–359 . September 2016 . 27687567 . 10.1080/21541248.2016.1235386 . 5997155 .
10. Oehlke O, Martin HW, Osterberg N, Roussa E . Rab11b and its effector Rip11 regulate the acidosis-induced traffic of V-ATPase in salivary ducts . Journal of Cellular Physiology . 226 . 3 . 638–51 . March 2011 . 20717956 . 10.1002/jcp.22388 . 10428914 .
11. Zhang X, Jiang S, Mitok KA, Li L, Attie AD, ((Martin TFJ)) . BAIAP3, a C2 domain-containing Munc13 protein, controls the fate of dense-core vesicles in neuroendocrine cells . The Journal of Cell Biology . 216 . 7 . 2151–2166 . July 2017 . 28626000 . 10.1083/jcb.201702099 . 5496627 .